It has been recognized for some time that human blood may be conditioned through dialytic action with a selected exchange fluid.
Dialysis is performed on patients whose kidneys are not capable of adequate purification of blood and elimination of excess water. This is usually accomplished by circulating a portion of the patient's blood through a dialysis cell in which the patient's blood passes on one side of a semi-permeable membrane and a dialysate solution on the other side thereof. The semi-permeable membrane passes waste materials and water from the patient's blood to the dialysate.
Dialysis is literally a life-saving process; however, sometimes undesirable side effects such as hypotension, fatigue, nausea, and the like, are encountered. Research is continuing to counter the adverse side effects and to further improve the efficacy of hemodialysis, including investigations to improve the composition of the exchange fluid, i.e., the composition of the dialysate.
A dialysate is an aqueous solution of an alkalizing salt. In the early days of dialysis sodium bicarbonate was used as the alkalizing agent. Subsequently, sodium acetate was substituted for sodium bicarbonate as the alkalizing agent since sodium acetate metabolizes in the patient's body to sodium bicarbonate and also because aqueous sodium acetate solutions are more easily maintainable in a sterile condition.
With the advent of more efficient, large-surface area dialysis equipment, undesirable side effects have been observed when sodium acetate-based dialysates are utilized, however. For example, in Graefe et al., "Less Dialysis-Induced Morbidity and Vascular Instability with Bicarbonate in Dialyzate," Annals of Internal Medicine 88:332-336 (1978), it is disclosed that a sodium bicarbonate-containing dialysate causes less nausea, headache, vomiting, post-dialysis fatigue, hypotension, disorientation and dizziness than a sodium acetate-containing dialysate when used in a high-efficiency, large-surface area dialyzer. Additionally, a beneficial effect of a sodium bicarbonate-containing dialysate in reducing the incidence of atherosclerosis is recognized in Kluge et al., Int. Soc. Art. Arg. 3A, p. 23 (April 1979).
The foregoing articles suggest that sodium bicarbonate, rather than sodium acetate, should be the alkalizing agent of choice for dialysates. However, aqueous sodium bicarbonate solutions, unlike aqueous sodium acetate solutions, are not self-sterilizing and thus may present sterility problems when prepared in advance of dialysis.
A unique solution to the foregoing problem is proposed in our copending U.S. patent application U.S. Ser. No. 048,575, filed on June 14, 1979 but abandoned in favor of U.S. Ser. No. 209,742, filed on Nov. 24, 1980 that matured into U.S. Pat. No. 4,326,955 on Apr. 27, 1982, to wit, the generation of an aqueous, bicarbonate ion-containing dialysate on demand from bacteriostatic, stable aqueous solutions just prior to dialysis. In particular, sodium bicarbonate solution is generated in situ by the interaction of an aqueous sodium carbonate solution with an aqueous acid solution containing a dissolved acid which is a member of the group consisting of hydrochloric acid (HCl), acetic acid (HAc), and mixtures thereof. The formulation of sodium bicarbonate proceeds by the following steps: ##STR1##
When a sodium bicarbonate-containing dialysate is prepared in the foregoing manner, it is desirable to have an effective and reliable means for metering and combining the respective starting acid and carbonate solutions to produce the sodium bicarbonate-containing dialysate. To this end the present invention provides a proportioning system that is eminently suitable for in situ generation of a bicarbonate-containing dialysate.